title: The combined effect of retinoic acid and LSD1 siRNA inhibition on cell death in the human neuroblastoma cell line SH-SY5Y.
abstract: OBJECTIVE
  Retinoic acid (RA) is used pharmacologically to treat neuroblastoma (NB), but its mechanism of action is unclear and it has limited use against refractory disease. This study investigated the expression of LSD1 (also known as KDM1A) in tumors, and assessed the efficacy of combining RA treatment with the inhibition of LSD1 expression.
  
  
  METHODS
  LSD1 protein expression levels were assessed semi-quantitatively in specimens of NB and ganglioneuroblastoma (GNB), along with the apoptosis markers, Bcl-2 and Bax. The combined effect of RA and LSD1 siRNA inhibition on cell death was then assessed in the human neuroblastoma cell line, SH-SY5Y.
  
  
  RESULTS
  LSD1 expression was higher in NB compared to GNB, and LSD1 overexpression directly correlated with Bcl-2 expression and inversely correlated with Bax expression. RA treatment or LSD1 siRNA inhibition alone inhibited the growth of SH-SY5Y cells, but did not cause significant apoptosis or cell death. Combined treatment led to higher rates of SH-SY5Y cell death, as reflected by an increased Bax/Bcl-2 ratio.
  
  
  CONCLUSIONS
  The combined effect of RA and LSD1 siRNA inhibition had a synergistic effect on promoting the apoptosis of NB cells. This novel approach may improve the clinical treatment of NB.
authors.affiliation: Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Xu
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jimeng
authors.initials: J
authors.lastname: Hu
authors.forename: Lili
authors.initials: L
authors.lastname: Xing
authors.forename: Ou
authors.initials: O
authors.lastname: Zhao
authors.forename: Yeming
authors.initials: Y
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D014212:Tretinoin; D056466:Histone Demethylases; C495195:KDM1A protein, human